Phytochemical determination and mechanistic investigation of Polygala tenuifolia root (Yuanzhi) extract for bronchitis: UPLC-MS/MS analysis, network pharmacology and in vitro/in vivo evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Bronchitis is a respiratory disease characterized by a productive cough. Polygala tenuifolia Willd., commonly known as Yuan zhi, is a traditional Chinese herbal medicine used for relieving cough and removing phlegm. Despite its historical use, studies are lacking on the effectiveness of P. tenuifolia in treating bronchitis. Furthermore, the molecular mechanisms underlying the action of its bioactive compounds remain unknown. AIM OF THE STUDY: This study aims to identify the main bioactive compounds responsible for the effects of P. tenuifolia liquid extract (PLE) in treating bronchitis and to elucidate the associated molecular mechanisms. MATERIALS AND METHODS: The main chemical compounds in PLE were identified and determined using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The antitussive, expectorant and anti-inflammatory activities of PLE were evaluated in an ammonia-induced mouse cough model, a tracheal phenol red excretion mouse model, and a xylene-induced ear swelling mouse model, respectively. A network pharmacology analysis was conducted to investigate the associated gene targets, gene ontology, and KEGG pathways related to the main bioactives in PLE targeting bronchitis. PLE and its five bioactive compounds were assessed for their potential anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Western blot analysis was conducted to elucidate the associated molecular mechanisms. RESULTS: Thirty-seven compounds in PLE were identified, and twelve main compounds were further quantified in PLE using UPLC-MS/MS. PLE oral gavage administrations (0.6 and 0.12 mg/kg) for 7 days markedly reduced cough frequency, prolonged latency period of cough, reduced phlegm and inflammation in mice. The network pharmacology analysis identified 57 gene targets of PLE against bronchitis. The PI3K/AKT and MAPK signalling pathways were the top two modulated pathways. In RAW264.7 cells, PLE (12.5-50 µg/mL) significantly reduced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. PLE downregulated LPS-elevated protein targets in both PI3K/AKT and MAPK signaling pathways. In PLE, tenuifolin, polygalaxanthone ⅠⅠⅠ, polygalasaponin ⅩⅩⅤⅢ, tenuifoliside B, and 3,6'-Disinapoyl sucrose, were identified as the top five core components responsible for treating bronchitis. These compounds were also found to modulate the protein targets in the PI3K/AKT and MAPK signalling pathways. CONCLUSIONS: This study demonstrated the potential therapeutic effects of PLE on bronchitis by reducing cough, phlegm and inflammation. The anti-inflammatory action and molecular mechanisms of the 5 main bioactive compounds in PLE were partly validated through the in vitro assays. The findings provide valuable insights into the mechanisms underlying the traditional use of PLE for bronchitis.

A Secure and Interpretable AI for Smart Healthcare System: A Case Study on Epilepsy Diagnosis Using EEG Signals.

The efficient patient-independent and interpretable framework for electroencephalogram (EEG) epileptic seizure detection (ESD) has informative challenges due to the complex pattern of EEG nature. Automated detection of ES is crucial, while Explainable Artificial Intelligence (XAI) is urgently needed to justify the model detection of epileptic seizures in clinical applications. Therefore, this study implements an XAI-based computer-aided ES detection system (XAI-CAESDs), comprising three major modules, including of feature engineering module, a seizure detection module, and an explainable decision-making process module in a smart healthcare system. To ensure the privacy and security of biomedical EEG data, the blockchain is employed. Initially, the Butterworth filter eliminates various artifacts, and the Dual-Tree Complex Wavelet Transform (DTCWT) decomposes EEG signals, extracting real and imaginary eigenvalue features using frequency domain (FD), time domain (TD) linear feature, and Fractal Dimension (FD) of non-linear features. The best features are selected by using Correlation Coefficients (CC) and Distance Correlation (DC). The selected features are fed into the Stacking Ensemble Classifiers (SEC) for EEG ES detection. Further, the Shapley Additive Explanations (SHAP) method of XAI is implemented to facilitate the interpretation of predictions made by the proposed approach, enabling medical experts to make accurate and understandable decisions. The proposed Stacking Ensemble Classifiers (SEC) in XAI-CAESDs have demonstrated 2% best average accuracy, recall, specificity, and F1-score using the University of California, Irvine, Bonn University, and Boston Children's Hospital-MIT EEG data sets. The proposed framework enhances decision-making and the diagnosis process using biomedical EEG signals and ensures data security in smart healthcare systems.

A subunit vaccine based on Brucella rBP26 induces Th1 immune responses and M1 macrophage activation.

Brucellosis is a global zoonotic infection caused by Brucella bacteria, which poses a significant burden on society. While transmission prevention is currently the most effective method, the absence of a licenced vaccine for humans necessitates the urgent development of a safe and effective vaccine. Recombinant protein-based subunit vaccines are considered promising options, and in this study, the Brucella BP26 protein is expressed using prokaryotic expression systems. The immune responses are evaluated using the well-established adjuvant CpG-ODN. The results demonstrate that rBP26 supplemented with a CpG adjuvant induces M1 macrophage polarization and stimulates cellular immune responses mediated by Th1 cells and CD8 + T cells. Additionally, it generates high levels of rBP26-specific antibodies in immunized mice. Furthermore, rBP26 immunization activates, proliferates, and produces cytokines in T lymphocytes while also maintaining immune memory for an extended period of time. These findings shed light on the potential biological function of rBP26, which is crucial for understanding brucellosis pathogenesis. Moreover, rBP26 holds promise as an effective subunit vaccine candidate for use in endemic areas.

Omics-based investigation of pathological liver injury induced by Echinococcus multilocularis infection in mice.

BACKGROUND: Alveolar echinococcosis (AE) can cause severe liver injury and be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver injury. Therefore, by exploring the changes of gene proteins in mice with damaged liver, we attempted to identify the key molecules of liver damage, and provide data that will enable the development of drugs targeting hepatic AE. METHODS: BALB/c mice were inoculated with protoscoleces via the hepatic portal vein. Three months later, B-ultrasound examination and Hematoxylin-eosin (H&E) staining were used to confirm liver damage in mice. RNA sequencing and Liquid chromatography-mass spectrometry (LC-MS) were used to screen differentially expressed molecules associated with liver damage through bioinformatics, and Quantitative Real-Time PCR (qRT-PCR) was used to verify their expression. RESULTS: B-ultrasound examination showed liver lesions in the infected group, and H&E staining showed liver inflammation, fibrosis and liver necrosis. RNA sequencing and LC-MS results showed changes in the levels of more than 1000 genes and proteins, with upregulation of immune and inflammation pathways. By contrast, the downregulated genes and proteins were mostly involved in various metabolic reactions. Correlation analysis was conducted between the transcriptome data and proteome data. The results revealed 240 differentially expressed genes, of which 192 were upregulated, and 48 were downregulated. Many of these genes were involved in metabolic reactions, such as Catalase (Cat), fatty acid synthase (Fasn), and IL-16 genes, which may have relevance to liver injury. The results of qRT-PCR were consistent with those of bioinformatics analysis. CONCLUSIONS: The mechanisms of liver injury in mice infected with Echinococcus multilocularis are complex, involving abnormal metabolism, oxidative stress, inflammatory response, and many other factors. This study provides the data for preliminary exploration for the development of targeted therapies against AE.

Adhesive Carbon Paste Electrode for Convenient and Long-term Electrocardiogram Monitoring: A Pilot Study.

Long-term electrocardiogram (ECG) monitoring is an important and widely-used technique in the clinic that helps with the diagnosis of possible diseases that cannot be detected in a short time monitoring. However, the clinically used electrode needs conductive gel to reduce the impedance between the skin and the electrodes, which easily causes the possibility of allergy. Moreover, as the conductive gel becomes dry, the signal's quality will decrease accordingly. In this paper, we proposed a novel adhesive Carbon Paste Electrode (CPE) to achieve convenient and long-term ECG monitoring. By comparing the time-domain waveforms, the R-R peak intervals difference, and the Signal-to-Noise Ratio (SNR) of ECG with the traditional conductive gel-based electrode (Gel) in fixed and unfixed conditions, the performance of the proposed CPE was investigated. The results showed that the CPE could achieve similar ECG monitoring both in fixed and unfixed conditions. When on Day 2, the quality acquired by Gel began to decrease while CPE was still stable, which was obvious especially in unfixed condition. The R-R peak intervals showed that on Day 2, the Gel was unreliable with some abnormal points occurring. Besides, the results of SNR and average heart rate (AHR) also confirmed that the CPE could achieve similar results as Gel on Day 1 and outperformed Gel on Day 2. It is believed that the proposed CPE opens a window of high-quality long-term ECG monitoring with more convenience.

Changes in intestinal flora of mice induced by rEg.P29 epitope peptide vaccines.

OBJECTIVE: Cystic echinococcosis (CE), a zoonotic parasitic disease caused by Echinococcus granulosus, remains a public health and socioeconomic issue worldwide, making its prevention and treatment of vital importance. The aim of this study was to investigate changes in the intestinal microbiota of mice immunized with three peptide vaccines based on the recombinant antigen of E. granulosus, P29 (rEg.P29), with the hope of providing more valuable information for the development of vaccines against CE. METHODS: Three peptide vaccines, rEg.P29T , rEg.P29B , and rEg.P29T + B , were prepared based on rEg.P29, and a subcutaneous immunization model was established. The intestinal floras of mice in the different immunization groups were analyzed by 16 S rRNA gene sequencing. RESULTS: The intestinal microbiota analysis at both immunization time points revealed that Firmicutes, Bacteroidota, and Verrucomicrobiota were the predominant flora at the phylum level, while at the genus level, Akkermansia, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and uncultured_rumen bacterium were the dominant genera. Some probiotics in the intestines of mice were significantly increased after immunization with the peptide vaccines, such as Lactobacillus_taiwanensis, Lactobacillus_reuteri, Lachnospiraceae_NK4A136_group, Bacteroides_acidifaciens, and so forth. Meanwhile, some harmful or conditionally pathogenic bacteria were decreased, such as Turicibacter sanguinis, Desulfovibrio_fairfieldensis, Clostridium_sp, and so forth, most of which are associated with inflammatory or infectious diseases. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis revealed that the differential flora were enriched in multiple metabolic pathways, primarily biological systems, human diseases, metabolism, cellular processes, and environmental information processing. CONCLUSION: In this study, we comprehensively analyzed and compared changes in the intestinal microbiota of mice immunized with three peptide vaccines as well as their related metabolic pathways, providing a theoretical background for the development of novel vaccines against E. granulosus.

To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer based on network pharmacology combined with LC-MS.

OBJECTIVE: To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology and LC-MS technology. METHODS: The effective components in Maiwei Dihuang decoction were detected by liquid chromatography-mass spectrometry (LC-MS). Use the SuperPred database to collect the relevant targets of the active ingredients of Mai Wei Di Tang, and then collect the relevant targets of non-small cell lung cancer from GeneCards, DisgenNET and OMIM databases. On this basis, PPI network construction, GO enrichment analysis and KEGG pathway annotation analysis were carried out for target sites. Finally, AutoDock Vina is used for molecular docking. RESULTS: We further screened 16 effective Chinese herbal compounds through LC-MS combined with ADME level. On this basis, we obtained 77 core targets through protein interaction network analysis. Through GO, KEGG analysis and molecular docking results, we finally screened out the potential targets of Maiwei Dihuang Decoction for NSCLC: TP53, STAT3, MAPK3. CONCLUSION: Maiwei Dihuang decoction may play a role in the treatment of NSCLC by co-regulating TP53/STAT3/MAPK3 signal pathway.

Long-term weathering difference in soil-like indicators of bauxite residue mediates the multifunctionality driven by microbial communities.

Long-term weathering enhances the stability of ecosystem services and alters the microbiome, however, its influences on the relationship between microbial diversity and multifunctionality are still poorly understood. Hereby, 156 samples (0-20 cm) from five artificially divided functional zones including central bauxite residue zone (BR), the zone near residential area (RA), the zone near dry farming area (DR), the zone near natural forest area (NF), and the zone near grassland and forest area (GF) were collected in a typical disposal area to determine the heterogeneity and development of biotic and abiotic properties of bauxite residue. Residues in BR and RA exhibited higher values of pH, EC, heavy metals, and exchangeable sodium percentage compared to those in NF and GF. Our results showed a positive correlation between multifunctionality and soil-like quality during long-term weathering. Microbial diversity and microbial network complexity responded positively to multifunctionality within the microbial community, which was parallel with ecosystem functioning. Long-term weathering promoted oligotrophs-dominated bacterial assemblages (mostly Acidobacteria and Chloroflexi) and suppressed copiotrophs (including Proteobacteria and Bacteroidota), while the response of fungal communities was lower. Rare taxa from bacterial oligotrophs were particularly important at the current stage for maintaining ecosystem services and ensuring microbial network complexity. Our results underscore the significance of microbial ecophysiological strategies in response to changes in multifunctionality during long-term weathering, and highlight the necessity of conserving and augmenting the abundance of rare taxa to ensure the stable provision of ecosystem functions in bauxite residue disposal areas.

High-Density Surface Electromyography for Swallowing Evaluation in Post-Radiation Dysphagia.

OBJECTIVES: Our study aimed to investigate the feasibility of using high-density surface electromyography (HD-sEMG) for swallowing assessment by comparing the quantitative parameters and topographic patterns of HD-sEMG between post-irradiated patients and healthy individuals. METHODS: Ten healthy volunteers and ten post-irradiated nasopharyngeal carcinoma patients were recruited. 96-channel HD-sEMG was recorded although each participant consumed different consistencies of food (thin and thick liquid, puree, congee, and soft rice). Dynamic topography was generated from the root mean square (RMS) of the HD-sEMG signals to illustrate the anterior neck muscle function in the swallowing process. The averaged power of muscles and the symmetry of swallowing patterns were assessed by objective parameters including average RMS, Left/Right Energy Ratio, and Left/Right Energy Difference. RESULTS: The study showed different swallowing patterns between patients with dysphagia and healthy individuals. The mean RMS values were higher in the patient group compared to the healthy group, but the difference was not statistically significant. Asymmetrical patterns were shown in patients with dysphagia. CONCLUSION: HD-sEMG is a promising technique that could be used to quantitatively evaluate the average power of neck muscles and the symmetry of swallowing activities in patients with swallowing difficulties. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:2920-2928, 2023.

Hairy-Skin-Adaptive Viscoelastic Dry Electrodes for Long-Term Electrophysiological Monitoring.

Long-term epidermal electrophysiological (EP) monitoring is crucial for disease diagnosis and human-machine synergy. The human skin is covered with hair that grows at an average rate of 0.3 mm per day. This impedes a stable contact between the skin and dry epidermal electrodes, resulting in motion artifacts during ultralong-term EP monitoring. Therefore, accurate and high-quality EP signal detection remains challenging. To address this issue, a new solution-the hairy-skin-adaptive viscoelastic dry electrode (VDE) is reported. This innovative technology is capable of bypassing hair and filling into the skin wrinkles, leading to long-lasting and stable interface impedance. The VDE maintains a stable interface impedance for a remarkable period of 48 days and 100 cycles. The VDE is highly effective in shielding against hair disturbances in electrocardiography (ECG) monitoring, even during intense chest expansion, and in electromyography (EMG) monitoring during large strain. Furthermore, the VDE is easily attachable to the skull without requiring any electroencephalogram (EEG) cap or bandage, making it an ideal solution for EEG monitoring. This work represents a substantial breakthrough in the field of EP monitoring, providing a solution for the previously challenging issue of monitoring human EP signals on hairy skin.

Immunogenicity of peptide-based vaccine composed of epitopes from Echinococcus granulosus rEg.P29.

Echinococcus granulosus is one of the main causes of economic loss in the livestock industry because of its food-borne transmission. Cutting off the transmission route is a valid prevention method, and vaccines are the most effective means of controlling and eliminating infectious diseases. However, no human-related vaccine has been yet marketed. As a genetic engineering vaccine, recombinant protein P29 of E. granulosus (rEg.P29) could provide protection against deadly challenges. In this study, we generated peptide vaccines (rEg.P29T , rEg.P29B , and rEg.P29T+B ) based on rEg.P29 and an immunized model was established by subcutaneous immunization. Further evaluation showed that peptide vaccine immunization in mice induced T helper type 1 (Th1)-mediated cellular immune responses, leading to high levels of rEg.P29 or rEg.P29B -specific antibodies. In addition, rEg.P29T+B immunization can induce a higher antibody and cytokine production level than single-epitope vaccines, and immune memory is also longer. Collectively, these results suggest that rEg.P29T+B has the potential to be developed as an efficient subunit vaccine for use in areas where E. granulosus is endemic.

[A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent]. / 基于亚低温床垫与高压氧舱结合的新生儿智能调控系统.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Towards Optimizing the Quality of Long-Term Physiological Signals Monitoring by Using Anhydrous Carbon Paste Electrode.

Long-term physiological signal monitoring is very important for the diagnosis of health conditions that occur randomly and cannot be easily detected by a short period of a hospital visit. However, the conventional wet electrodes suffered from the problem of signal quality degradation due to the gradual dehydration of the conductive gel. An anhydrous carbon paste electrode (CPE) constructed by a composite of carbon black and polydimethylsiloxane was proposed to enable long-term physiological signal monitoring without signal quality degradation as time elapses. The performance was systematically compared with conventional electrodes when measuring long-term physiological signals including electrocardiogram (ECG), electromyogram (EMG), electroencephalogram (EEG) and auditory brainstem response (ABR). The proposed CPE showed more stable skin-electrode impedance and higher signal qualities as the monitoring time increased up to 48 days, with signal-to-noise ratios (SNRs) of 16.43 ± 10.39 dB higher for ECG and 24.30 ± 7.79 dB higher for EMG when compared with wet electrodes. The CPE method could also obtain more consistent ABR waveform morphologies and could measure EEG under sweating conditions. It is believed that the proposed CPE could be a potential candidate for durable and robust wearable sensors systems on long-term physiological signal monitoring.

Recombinant antigen P29 of Echinococcus granulosus induces Th1, Tc1, and Th17 cell immune responses in sheep.

Echinococcosis is a common human and animal parasitic disease that seriously endangers human health and animal husbandry. Although studies have been conducted on vaccines for echinococcosis, to date, there is no human vaccine available for use. One of the main reasons for this is the lack of in-depth research on basic immunization with vaccines. Our previous results confirmed that recombinant antigen P29 (rEg.P29) induced more than 90% immune protection in both mice and sheep, but data on its induction of sheep-associated cellular immune responses are lacking. In this study, we investigated the changes in CD4+ T cells, CD8+ T cells, and antigen-specific cytokines IFN-γ, IL-4, and IL-17A after rEg.P29 immunization using enzyme-linked immunospot assay (ELISPOT), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to investigate the cellular immune response induced by rEg.P29 in sheep. It was found that rEg.P29 immunization did not affect the percentage of CD4+ and CD8+ T cells in peripheral blood mononuclear cells (PBMCs), and was able to stimulate the proliferation of CD4+ and CD8+ T cells after immunization in vitro. Importantly, the results of both ELISPOT and ELISA showed that rEg.P29 can induce the production of the specific cytokines IFN-γ and IL-17A, and flow cytometry verified that rEg.P29 can induce the expression of IFN-γ in CD4+ and CD8+ T cells and IL-17A in CD4+ T cells; however, no IL-4 expression was observed. These results indicate that rEg.P29 can induce Th1, Th17, and Tc1 cellular immune responses in sheep against echinococcosis infection, providing theoretical support for the translation of rEg.P29 vaccine applications.

Usefulness of phase gradients of otoacoustic emissions in auditory health screening: An exploration with swept tones.

Otoacoustic emissions (OAEs) are low-level sounds generated by the cochlea and widely used as a noninvasive tool to inspect cochlear impairments. However, only the amplitude information of OAE signals is used in current clinical tests, while the OAE phase containing important information about cochlear functions is commonly discarded, due to the insufficient frequency-resolution of existing OAE tests. In this study, swept tones with time-varying frequencies were used to measure stimulus frequency OAEs (SFOAEs) in human subjects, so that high-resolution phase spectra that are not available in existing OAE tests could be obtained and analyzed. The results showed that the phase of swept-tone SFOAEs demonstrated steep gradients as the frequency increased in human subjects with normal hearing. The steep phase gradients were sensitive to auditory functional abnormality caused by cochlear damage and stimulus artifacts introduced by system distortions. At low stimulus levels, the group delays derived from the phase gradients decreased from around 8.5 to 3 ms as the frequency increased from 1 to 10 kHz for subjects with normal hearing, and the pattern of group-delay versus frequency function showed significant difference for subjects with hearing loss. By using the swept-tone technology, the study suggests that the OAE phase gradients could provide highly sensitive information about the cochlear functions and therefore should be integrated into the conventional methods to improve the reliability of auditory health screening.

Alterations in Gut Microbiota Profiles of Mice Infected with Echinococcus granulosus sensu lato Microbiota Profiles of Mice Infected with E. granulosus s.l.

OBJECTIVE: Cystic echinococcosis is a kind of parasitic disease that seriously endangers human and animal health. At present, its prevention and treatment still do not achieve the desired results. The aims of this study were to explore the effect of CE on intestinal microflora in mice. METHODS: In this study, 16S rRNA metagenome sequencing and bioinformatics were used to analyze the intestinal flora of mice infected with E. granulosus s.l. Changes in intestinal microbial community abundance were investigated and the differences in microbial populations of mice infected with E. granulosus s.l. were screened. RESULTS: Our results show that at the phylum level, nine abundant taxa were identified, the relative abundance of Firmicutes and Proteobacteria were enriched in infected mice, whereas Bacteroidetes and Patescibacteria were enriched in control mice (P < 0.01). At the class level, 13 abundant taxa were identified, the relative abundance of Bacilli was enriched in control mice, but decreased in infected mice (P < 0.01). At the order level, 15 abundant taxa were identified, the relative abundance of Lactobacillales was enriched in control mice, but decreased in infected mice (P < 0.01). At the family level, 28 abundant taxa were identified, enriched bacteria in the infected mice was Streptococcaceae, while the enriched bacteria in the control group was Lactobacillaceae (P < 0.01). At the genus level, 79 abundant taxa were identified, enriched bacteria in the infected mice was Streptococcus, while the enriched bacteria in the control group was uncultured_bacterium_f_Eggerthellaceae (P < 0.01). At the species level, 80 abundant taxa were identified, enriched bacteria in the infected mice was uncultured_bacterium_g_Streptococcus, while the enriched bacteria in the control group was uncultured_bacterium_f_Eggerthellaceae (P < 0.01). 39 KEGG pathways were identified that were differentially enriched between the infected and control mice. CONCLUSION: This study comprehensively demonstrates the differential intestinal microbiota of infected mice and analyzes the metabolic pathways related to the specific microbiota. This could provide new targets and research direction for the treatment and prevention of diseases caused by E. granulosus s.l.

Towards Evaluating Pitch-Related Phonation Function in Speech Communication Using High-Density Surface Electromyography.

Pitch, as a sensation of the sound frequency, is a crucial attribute toward constructing a natural voice for communication. Producing intelligible sounds with normal pitches depend on substantive interdependencies among facial and neck muscles. Clarifying the interrelations between the pitches and the corresponding muscular activities would be helpful for evaluating the pitch-related phonating functions, which would play a significant role both in training pronunciation and in assessing dysphonia. In this study, the speech signals and the high-density surface electromyography (HD sEMG) signals were synchronously acquired when phonating [a:], [i:], and [ә:] vowels with increasing pitches, respectively. The HD sEMG energy maps were constructed based on the root mean square values to visualize spatiotemporal characteristics of facial and neck muscle activities. Normalized median frequency (nMF) and root-mean square (nRMS) were correspondingly extracted from the speech and sEMG recordings to quantitatively investigate the correlations between sound frequencies and myoelectric characteristics. The results showed that the frame-wise energy maps built from sEMG recordings presented that the muscle contraction strength increased monotonously across pitch-rising, with left-right symmetrical distribution for the face/neck. Furthermore, the nRMS increased at a similar rate to the nMF when there were rising pitches, and the two parameters had a significant correlation across different vowel tasks [(a:) (0.88 ± 0.04), (i:) (0.89 ± 0.04), and (ә:) (0.87 ± 0.05)]. These findings suggested the possibility of utilizing muscle contraction patterns as a reference for evaluating pitch-related phonation functions. The proposed method could open a new window for developing a clinical approach for assessing the muscular functions of dysphonia.

Effect of Tanshinone IIA on Gut Microbiome in Diabetes-Induced Cognitive Impairment.

Diabetes-induced cognitive impairment (DCI) presents a major public health risk among the aging population. Previous clinical attempts on known therapeutic targets for DCI, such as depleted insulin secretion, insulin resistance, and hyperglycaemia have delivered poor patient outcomes. However, recent evidence has demonstrated that the gut microbiome plays an important role in DCI by modulating cognitive function through the gut-brain crosstalk. The bioactive compound tanshinone IIA (TAN) has shown to improve cognitive and memory function in diabetes mellitus models, though the pharmacological actions are not fully understood. This study aims to investigate the effect and underlying mechanism of TAN in attenuating DCI in relation to regulating the gut microbiome. Metagenomic sequencing analyses were performed on a group of control rats, rats with diabetes induced by a high-fat/high-glucose diet (HFD) and streptozotocin (STZ) (model group) and TAN-treated diabetic rats (TAN group). Cognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neurological biomarkers. The fasting blood glucose (FBG) level was monitored throughout the experiments. The levels of serum lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level. The morphology of the colon barrier was observed by histopathological staining. Our study confirmed that TAN reduced the FBG level and improved the cognitive and memory function against HFD- and STZ-induced diabetes. TAN protected the endothelial tight junction in the hippocampus and colon, regulated neuronal biomarkers, and lowered the serum levels of LPS and TNF-α. TAN corrected the reduced abundance of Bacteroidetes in diabetic rats. At the species level, TAN regulated the abundance of B. dorei, Lachnoclostridium sp. YL32 and Clostridiodes difficile. TAN modulated the lipid metabolism and biosynthesis of fatty acids in related pathways as the main functional components. TAN significantly restored the reduced levels of isobutyric acid and butyric acid. Our results supported the use of TAN as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome regulation.

Towards high-accuracy classifying attention-deficit/hyperactivity disorders using CNN-LSTM model.

Objective. The neurocognitive attention functions involve the cooperation of multiple brain regions, and the defects in the cooperation will lead to attention-deficit/hyperactivity disorder (ADHD), which is one of the most common neuropsychiatric disorders for children. The current ADHD diagnosis is mainly based on a subjective evaluation that is easily biased by the experience of the clinicians and lacks the support of objective indicators. The purpose of this study is to propose a method that can effectively identify children with ADHD.Approach. In this study, we proposed a CNN-LSTM model to solve the three-class problems of classifying ADHD, attention deficit disorder (ADD) and healthy children, based on a public electroencephalogram (EEG) dataset that includes event-related potential (ERP) EEG signals of 144 children. The convolution visualization and saliency map methods were used to observe the features automatically extracted by the proposed model, which could intuitively explain how the model distinguished different groups.Main results. The results showed that our CNN-LSTM model could achieve an accuracy as high as 98.23% in a five-fold cross-validation method, which was significantly better than the current state-of-the-art CNN models. The features extracted by the proposed model were mainly located in the frontal and central areas, with significant differences in the time period mappings among the three different groups. The P300 and contingent negative variation (CNV) in the frontal lobe had the largest decrease in the healthy control (HC) group, and the ADD group had the smallest decrease. In the central area, only the HC group had a significant negative oscillation of CNV waves.Significance. The results of this study suggest that the CNN-LSTM model can effectively identify children with ADHD and its subtypes. The visualized features automatically extracted by this model could better explain the differences in the ERP response among different groups, which is more convincing than previous studies, and it could be used as more reliable neural biomarkers to help with more accurate diagnosis in the clinics.

Flexible Non-contact Electrodes for Wearable Biosensors System on Electrocardiogram Monitoring in Motion.

Electrocardiogram (ECG) is a critical physiological indicator that contains abundant information about human heart activities. However, it is a kind of weak low-frequency signal, which is easy to be interfered by various noises. Therefore, wearable biosensors (WBS) technique is introduced to overcome this challenge. A flexible non-contact electrode is proposed for wearable biosensors (WBS) system, which is made up of flexible printed circuits materials, and can monitor the ECG signals during exercise for a long time. It uses the principle of capacitive coupling to obtain high-quality signals, and reduces the impact of external noise through active shielding; The results showed that the proposed non-contact electrode was equivalent to a medical wet electrode. The correlation coefficient was as high as 99.70 ± 0.30% when the subject was resting, while it was as high as 97.53 ± 1.80% during exercise. High-quality ECG could still be collected at subjects walking at 7 km/h. This study suggested that the proposed flexible non-contact electrode would be a potential tool for wearable biosensors for medical application on long-term monitoring of patients' health and provide athletes with physiological signal measurements.